The distinguished Emeriti faculty of the Biological Chemistry Department have been widely viewed as some of the best scientist in their field. Emeriti faculty continue to pursue their scientific endeavors while providing important insight and guidance to the next generation of scientists. We regard the Emeriti faculty in our departm​ent as not only a marker of what we have been able to accomplish as a department but as a key component to our continued success.​​​​​​

Paul EnglundProfessor Emeritus of Biological Chemistry
Johns Hopkins University School of Medicine

Program Description

Our laboratory is investigating the biology of trypanosomes, protozoan parasites responsible for important tropical diseases. We focus on two areas:

Kinetoplast DNATrypanosome mitochondrial DNA consists of several thousand DNA rings topologically interlocked in a giant DNA network. We are studying the novel mechanism by which kinetoplast DNA replicates, the structure of isolated kinetoplast DNA, and the complex structural organization of this network in vivo. Much of our current work concerns the identification and study the proteins involved in kDNA replication and maintenance.

Trypanosome fatty acid synthesisTrypanosomes have an abundant GPI-anchored protein named variant surface glycoprotein. This GPI anchor is unusual in that it contains the fatty acid myristate. In studies on the origin of myristate, we discovered a robust fatty acid synthesis system whose major product is myristate (even though it was thought for 30 years that these parasites cannot make any fatty acid). In an investigation of the machinery for fatty acid synthesis we discovered a novel and unprecedented mechanism. Instead of using a conventional type I or type II synthase, found in all other cells, trypanosomes use microsomal elongases to make fatty acids de novo. They also have a type II fatty acid synthase in the mitochondria.

Albert MildvanProfessor Emeritus of Biological Chemistry
Johns Hopkins University School of Medicine

Program Description

To understand the structural basis for the high catalytic power of enzymes, we have studied the mechanisms of enzyme-catalyzed reactions of DNA (DNA Topoisomerase I, Staphylococcal nuclease, DNA polymerase) of ATP (Mut T dNTPase and related Nudix hydrolases) and enzyme-catalyzed polarization of carbonyl groups (ketosteroid isomerase 4-oxalocrotonate tautomerase). Multidimensional heteronuclear NMR, electron spin resonance, chemical and genetic modification of enzymes, and kinetic isotope effects are used to elucidate the structures of enzymes, the role of metals, and the conformations, locations, arrangement, and exchange rates of enzyme-bound substrates. The solution structures of enzymes are determined by ultra-high resolution 1D, 2D and 3D NMR methods. We are currently studying the roles of divalent cations in the mechanism of Methionine aminopeptidase, in collaboration with Professor Jun O. Liu, Department of Pharmacology and Molecular Sciences.

Barbara Sollner-WebbProfessor Emeritus of Biological Chemistry
Johns Hopkins University School of Medicine

Program Description

Although over 10,000 papers use transient transfection, no one had looked where this DNA goes; its investigation has led to the discovery of an unprecedented sequence-specific DNA localization process that evidently also function on the cell's chromosomal DNA. It turns out that transiently transfected mammalian cells take up thousands of plasmid molecules, and they can self-associate and localize to particular subnuclear sites, in a promoter-specific manner. Plasmids bearing RNA pol I transcriptional control elements (rRNA gene promoters, enhancers, or terminators) target to sites within nucleoli, juxtaposed to the cell's rRNA genes; plasmids bearing pol III promoters target to novel peri-nucleolar sites where the cell's 5S RNA genes turn out to reside; and plasmids bearing pol II promoters go to nucleoplasmic foci, preferentially juxtaposed to chromosomal copies of those promoters. This localization does not require transcription, and can be reproduced in microinjected cells and in vitro using isolated nucleoli. This system provide a manipulatable method to study nuclear DNA localization, a topic that is receiving a much deal of attention in the recent literature (from 4C-based studies that reveal preferential locations of chromosomal genes but are not well-suited to investigating the underlying mechanism). Study of this promoter-specific localization promises to help explain how the eukaryotic cell organizes its chromosomal DNA.

In parallel, we have been studying RNA editing in trypanosomes, a fascinating form of RNA maturation in which U residues are specifically inserted into and deleted from primary transcripts, often in massive amounts, to generate mature mRNAs. We have purified a simple protein complex that actively catalyzes both U-insertional and U-deletional editing cycles, cloned their encoding genes, and optimized editing to increase U-deletion by 100 fold and U-insertion several fold. Toward elucidating the mechanism of this processing, we are biochemically analyzing the editing complex and genetically investigating (using classical knock-outs and RNAi) the genes encoding its components. Interestingly, the U-deletion and U-insertion use completely different catalytic components located in a common complex.